Pancreatic ductal adenocarcinoma (PDAC) is aggressive, with a 5-year survival rate of only 12.8%, and its increasing incidence in Western countries highlights the urgent need for better early-stage detection and treatment methods. Early diagnosis significantly improves the chances of survival, but non-specific symptoms and undetectable precursor lesions pose a major challenge. To date, there are no reliable screening tools to detect PDAC at an early stage. Herpesvirus entry mediator (HVEM) has already been proposed as a prognostic marker in numerous cancer types. Therefore, we investigated the role of HVEM in PDAC. Flow cytometry was used to analyze HVEM expression in immune cells and its inhibitory receptors (CD160 and BTLA) on T-cells, as well as its subsets in the peripheral blood of 57 diagnosed PDAC patients and 17 clinical controls. In addition, survival analyses were performed within the PDAC cohort, changes in HVEM expression were analyzed in relation to clinicopathological parameters, and a correlation analysis between HVEM expression and cytokine levels of IL-6 and IL-10 was conducted. Furthermore, HVEM expression on monocytes and their subsets was evaluated as a potential prognostic marker and compared with the prognostic utility of CA19-9. We found that HVEM expression is significantly elevated on immune cells, particularly on monocytes (p < 0.0001) and their subsets, in PDAC patients, and is associated with reduced survival (p = 0.0067) and clinicopathological features such as perineural, lymphovascular, and vascular invasion. Moreover, HVEM-expressing monocytes demonstrated superior predictive value compared to CA19-9, highlighting their potential as part of a combined screening tool for PDAC. In conclusion, HVEM on monocytes could serve as a novel prognostic marker for PDAC.

Circulating myeloid cells are critical regulators of pancreatic ductal adenocarcinoma (PDAC) progression. However, their postoperative dynamics and clinical relevance remain poorly defined. In a prospective longitudinal study, blood was collected from PDAC patients prior to surgery and on postoperative day 7. Flow cytometry was used to characterize monocytes, including classical (CM), intermediate (IMM), and non-classical (NCM) subsets, along with regulatory and co-stimulatory molecules (CD71, CD40, CD141, CD80, CD86, PD-L1). Cytokine levels (IL-6, IL-10, TNF-α, IL-1β) were quantified by ELISA and correlated with clinical parameters and survival. Total monocytes and CM increased significantly at day 7, whereas IMM and NCM decreased. CD71, CD141, CD80, and CD86 expression were significantly altered across subsets, with the most pronounced reduction observed in CD86 expressing NCM. CD86 expressing NCM correlated inversely with systemic bilirubin but not CEA, lymphocytes, thrombocytes, or hospital stay. IL-6 and IL-10 increased postoperatively; IL-10 showed a tendency toward inverse correlation with CD86⁺ NCM. Low CD86 expression on NCM at day 7 was associated with reduced survival and higher relapse probability. CD86 expression on NCMs is profoundly reduced after PDAC surgery and serves as a prognostic biomarker linked to inflammation, bilirubin metabolism, survival, and recurrence. Postoperative monocyte profiling may improve risk stratification and inform early clinical decision-making.